![]() ![]() This generates contractile forces and traction, allowing the cell body to move forward. 3 Typically, a migrating glioma cell remodels its cytoskeleton and forms protrusions and focal adhesions at the leading edge of the migratory front. This enables them to transform intracellular forces into net cell body translocation. To migrate, glioma cells must acquire a special asymmetric, and polarized phenotype. 2 Therefore, to improve our ability to treat patients with malignant gliomas, we must increase our understanding of the migratory and invasive properties of these tumors. Malignant gliomas are the most common primary brain tumors in adults 1 and are among the most aggressive malignant tumors in part because of their propensity to disseminate diffusely throughout the brain. CD99 may be an important future target to inhibit migration and invasion, especially in CD99-expressing gliomas. Moreover, CD99 might be involved in amoeboid-mesenchymal transition in glioma migration. Taken together, our findings suggest that CD99 may play an important role in the migration and invasion of human gliomas independent of Akt, ERK, or JNK signaling pathways. ![]() Interestingly, Rac activity was decreased and Rho activity was increased in CD99 overexpressing glioma cells, and the proportion of amoeboid cells to mesenchymal cells was significantly increased. An orthotopic brain tumor model demonstrates that CD99 overexpression significantly increases invasiveness and decreases survival rate. In contrast, when CD99 was overexpressed in glioma cells, we observed enhancement of cell migration and invasiveness. To assess the role of CD99 in glioma migration and invasion, we inhibited CD99 expression by siRNA and demonstrated decreased glioma migration and invasion. Using a tissue microarray, we validated that gliomas demonstrate higher expression of CD99 compared with nonneoplastic brain. In this study, our data reveal that only wild-type CD99 is expressed in human glioma cells and tissues. ![]() Previous studies have shown that wild-type CD99 may be an oncosuppressor in some tumors, distinct from the role of the splice variant isoform. CD99 has wild-type and splice variant isoforms. Although its function is not completely understood, CD99 is implicated in cell adhesion and migration in a variety of different cell types. Recently, gene expression profiling revealed that the transmembrane glycoprotein CD99 is more highly expressed in malignant glioma than in normal brain. The malignant glioma is the most common primary human brain tumor, and its migration and invasiveness away from the primary tumor mass are considered a leading cause of tumor recurrence and treatment failure. ![]()
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